Using sulfonylureas as a first-line treatment for diabetes is associated with an increased risk for cardiovascular disease (CVD) events or death compared with the use of metformin, research shows.
Sulfonylureas were associated with a significant 21% increased risk for acute myocardial infarction (MI), stroke, or death, a result that was consistent for glyburide and glipzide.
"The findings do not clarify whether the difference in CVD risk is due to harm from sulfonylureas, benefit from metformin, or both," write researcher Christianne Roumie (Vanderbilt University, Nashville, Tennessee, USA) and colleagues in the Annals of Internal Medicine.
In an editorial, Steven Nissen (Cleveland Clinic, Ohio, USA) says the findings could have implications for millions of patients with diabetes worldwide, but cautioned that the results need to be replicated and confirmed.
"With more than two thirds of diabetic patients dying of CV causes and millions of patients currently receiving sulfonylureas, this question must be resolved with high-quality evidence," writes Nissen.
The retrospective cohort study compared the effects of sulfonylureas and metformin on hard clinical outcomes using data from the National Veterans Health Administration databases.
In total, 253,690 patients initiated treatment, including 98,665 individuals taking a sulfonylurea and 155,025 taking metformin.
The crude rate of acute MI, stroke, or death was 18.2 per 1000 person-years among those treated with a sulfonylurea and 10.4 per 1000 person-years for those who received metformin.
After adjusting for multiple variables, treatment with a sulfonylurea translated into an excess of 2.2 CVD events or death per 1000 person-years, or a 21% increased risk, compared with metformin.
"These observations support the use of metformin for first-line diabetes therapy and strengthen the evidence about the cardiovascular advantages of metformin compared with sulfonylureas," conclude Roumie and colleagues.
The results were comparable in all subgroups.
To date, there has been limited data examining the CV effects of diabetes treatments. US regulatory policy has only required evidence that drugs used in diabetes lower blood glucose levels without affecting safety.
This changed, however, in 2008 when the Food and Drug Administration required all drug companies to rule out CV harm with any new antidiabetic agent.
Sulfonylureas and metformin were approved prior to 2008 and as a result of the legacy period have not been required to clear such CV hurdles.
According to Nissen, the lack of financial incentive to perform comparative effectiveness studies of these two commonly approved therapies requires observational analyses such as the present study.
"Continued darkness is not an acceptable option," he writes.
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